A. Jon Stoessl, CM, MD, FRCPC, FAAN
Professor, Neurology; Canada Research Chair (Tier 1) in Parkinson's Disease; Director, Pacific Parkinson's Research Centre and National Parkinson Foundation Centre of Excellence; Acting Head, Division of Neurology
Our research program is multi- and inter-disciplinary and focused on 3 overarching questions about Parkinson's disease:
- What causes Parkinson's? The Centre has projects on occupational risk factors and through a longstanding collaboration with the Mayo Clinic, genetic causes of PD. Through our partnership with TRIUMF, we use positron emission tomography (PET) to study the natural history of dopamine cell loss in Parkinson's as well as mechanisms that the brain uses to compensate for this loss. We have a particular interest in studying populations at high risk of developing PD.
- What mechanisms contribute to the complications of longstanding PD and its treatment? We have several projects related to this and while the previous focus was on motor complications such as fluctuations in motor function and dyskinesias, we are now focusing on non-motor complications of PD, particularly depression, cognitive decline and impulse control disorders.
- How can we use PD as a model to better understand the role of dopamine in the normal brain? We have a particular interest in the role of dopamine in signaling reward and its relevance to depression, impulse control problems and the placebo effect. We have shown that the placebo effect in PD is mediated by dopamine release and suggested that this likely contributed to placebo effects in other conditions as well.
Our work is funded by Team Grant in Parkinson's Disease from CIHR, a Research Unit award from the Michael Smith Foundation for Health Research and a Centre grant from the Pacific Alzheimer Research Foundation, as well as numerous operating grants from CIHR and other agencies.
1. Lee CS, Samii A, Sossi V, Ruth TJ, Schulzer M, Holden JE, Wudel J, Pal PK, de la Fuente R, Calne DB, Stoessl AJ (2000). In vivo PET evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease. Annals of Neurology 47: 493-503.
2. de la Fuente-Fernandez R, Lu J-Q, Sossi V, Jivan S, Schulzer M, Holden JE, Lee CS, Ruth TJ, Calne DB, Stoessl AJ (2001). Biochemical variations in the synaptic level of dopamine precede motor fluctuations in Parkinson's disease: PET evidence for increased dopamine turnover. Annals of Neurology 49: 298-303.
3. de la Fuente-Fernandez R, Ruth TJ, Sossi V, Schulzer M, Calne DB, Stoessl AJ (2001). Expectation and Dopamine Release: Mechanism of the Placebo Effect in Parkinson's Disease. Science 293: 1164-1166.
4. de la Fuente-Fernandez R, Schulzer M, Stoessl AJ (2002). The placebo effect in neurological disorders. Lancet Neurology 1: 85-91.
5. de la Fuente-Fernandez R, Stoessl AJ (2002). The placebo effect in Parkinson's disease. Trends in Neurosciences 25: 302-306.
6. Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, Shannon KM, Nauert GM, Perl DP, Godbold J, Freeman TB (2003). A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Annals of Neurology 54: 403-414.
7. de la Fuente-Fernandez R, Schulzer M, Mak E, Calne DB, Stoessl AJ (2004). Presynaptic mechanisms of motor fluctuations in Parkinson's Disease: a probabilistic model. Brain 127: 888-899.
8. de la Fuente-Fernandez R, Schulzer M, Stoessl AJ (2004). Placebo mechanisms and reward circuitry: Clues from Parkinson's disease. Biological Psychiatry 56: 67-71.
9. de la Fuente-Fernandez R, Sossi V, Huang Z, Furtado S, Lu J-Q, Calne DB, Ruth TJ, Stoessl AJ (2004). Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson's disease: implications for dyskinesias. Brain 127: 2747-2754.
10. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Muller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T (2004). Mutations in LRRK2 cause autosomal dominant Parkinsonism with pleomorphic pathology. Neuron 44: 601-607.
11. Adams JR, van Netten H, Schulzer M, Mak E, McKenzie J, Strongosky A, Sossi V, Ruth TJ, Lee CS, Farrer M, Gasser T, Uitti RJ, Calne DB, Wszolek ZK, Stoessl AJ (2005). PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation. Brain 128: 2777-2785.
12. Lidstone S, Stoessl AJ (2006). Understanding the placebo effect: contributions from neuroimaging. Molecular Imaging in Biology 9: 176- 185.
13. Stoessl AJ (2007). Gene therapy for Parkinson's disease: early data. Lancet 369: 2056-2058 (invited editorial).
14. Sossi V, de la Fuente-Fernandez R, Schulzer M, Troiano A, Ruth TJ, Stoessl AJ (2007). Dopamine transporter relation to dopamine turnover in Parkinson disease: a PET study. Annals of Neurology 62: 468-475.
15. Nandhagopal R, McKeown MJ, Stoessl AJ (2008). Functional imaging in Parkinson's disease. Neurology 70: 1478-1488.
16. Martin WRW, Wieler M, Stoessl AJ, Schulzer M (2008). Dihydrotetrabenazine PET imaging in early untreated Parkinson's disease. Annals of Neurology 63: 388-394.
17. Stoessl AJ (2008). Potential therapeutic targets for Parkinson's disease. Expert Opinion on Therapeutic Targets 12: 425-436.
18. Marks WJ, Ostrem JL, Verhagen L, Starr PA, Bakay RAE, Taylor R, Cahn-Weiner DA, Stoessl AJ, Olanow CW, Bartus RT (2008). A Phase I, Open-Label Study of CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN]) to Assess the Safety and Tolerability of Intraputaminal Delivery to Subjects with Idiopathic Parkinson's Disease. Lancet Neurology 7: 400-408.
19. Nandhagopal R, Mak E, Schulzer M, McKenzie J, McCormick S, Sossi V, Ruth TJ, Strongosky A, Farrer MJ, Wszolek ZK, Stoessl AJ (2008). Progression of dopaminergic dysfunction in a LRRK2 kindred: a multitracer PET study. Neurology 71: 1790-1795.
20. Troiano AR, de la Fuente-Fernandez R, Sossi V, Schulzer M, Mak E, Ruth TJ, Stoessl AJ (2008). PET demonstrates reduced dopamine transporter expression in PD with dyskinesias. Neurology, available online (doi:10.1212/01.wnl.0000338631.73211.56).
21. Farrer MJ, Hulihan MM, Kachergus JM, Dachsel J, Stoessl AJ, Grantier LL, Calne S, Calne DB, Lechevalier B, Chapon F, Tsuboi Y, Yamada T, Gutmann L, Elibol E, Bhatia KP, Wider CW, Vilarino-Guell C, Ross OA, Brown LA, Catanedes-Casey M, Dickson DW, Wszolek ZK (2009). DCTN1 mutations in Perry syndrome. Nature Genetics, available online (doi:10.1038/ng.293).
22. Stoessl AJ (2009). Radionuclide scanning to diagnose Parkinson disease: is it cost effective? Nature Clinical Practice Neurology 5: 10-11.